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Synthesis, Biologic Effects, and Biochemical Properties of Some 2’-Azido- and 2’-Amino-2’-Deoxyarabinofuranosyl Pyrimidines and Purines

  • M. Bobek
  • Y.-C. Cheng
  • E. Mihich
  • A. Bloch
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 74)

Summary

Various 2’-azido- and 2’-aminoarabinofuranosyl purine and pyrimidine nucleosides have been synthesized. Among these, the derivatives of cytosine and of adenine inhibit the growth of some tumor cell lines in vitro and in vivo. 2’-Azidoarabinofuranosyl cytosine also interferes with the replication of herpes simplex virus types I and II. Whereas 2’-azidoara-C is resistant to deamination by a partially purified CdR deaminase from KB cells, the adenine derivatives are substrates for aminohydrolases partially purified from calf and mouse intestines. Both azido- and aminoara-C are phosphorylated by partially purified CdR kinases from leukemia L1210 and from human AML blast cells. The accumulated data encourage exploration of the clinical utility of the more potent of these analogues.

Keywords

Herpes Simplex Virus Type L1210 Cell Adenosine Deaminase Acute Myelocytic Leukemia Cell Azido Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Bobek, M (1979) 2’-Azido-2’-deoxy- and 2’-amino-2’-deoxy-D-arabinofuranosyl purine nucleosides. Carbohydr Res 70:263–273CrossRefGoogle Scholar
  2. 2.
    Bobek M, Bloch A, Berkowitz P, Bardos TJ (1977) Synthesis and antitumor activity of 1,2-dihydro-l-(2-deoxy-β-D-erythro-pentofuranosyl)-2-oxo-5-methylpyrazine 4-oxide, a structural analogue of thymidine. J Med Chem 20:458–460PubMedCrossRefGoogle Scholar
  3. 3.
    Bobek M, Cheng YC, Bloch A (1978) Novel arabinofuranosyl derivatives of cytosine resistant to enzymatic deamination and possessing potent antitumor activity. J Med Chem 21:597PubMedCrossRefGoogle Scholar
  4. 4.
    Bobek M, Martin V (1978) The synthesis of anomeric 3-0-acetyl-5-Obenzoyl-2-azi- do-2-deoxy-D-arabinofuranosyl chlorides. Versatile sugar intermediates for the synthesis of 2’-azido-2’-deoxy- and 2’-amino-2’-deoxy-β-D-arabinofuranosyl nucleosides. Tetrahedron Lett 22:1919–1922CrossRefGoogle Scholar
  5. 5.
    Cheng YC, Domin B, Lee LS (1977) Human deoxycytidine kinase. Purification and characterization of the cytoplasmic and mitochondrial isozymes derived from blast cells of acute leukemia patients. Biochem Biophys Acta 481:481–492Google Scholar
  6. 6.
    Cheng YC, Domin BA, Sharma RA, Bobek M (1976) Antiviral action and cellular toxicity of four thymidine analogues: 5-ethyl-, 5-vinyl-, 5-propyl-, and 5-allyl-2’-deoxyuridine. Antimicrob Agents Chemother 10:119–122PubMedGoogle Scholar
  7. 7.
    Ho DHW, Carter CF, Loo TL (1975) Tetrahydrouridine in the uptake and metabolism of arabinosylcytosine by human acute myelocytic leukemia cells. Proc Am Assoc Cancer Res 16:57Google Scholar
  8. 8.
    LePage GA, Worth LS, Kimball AP (1976) Enhancement of the antitumor activity of arabinofuranosyladenine by 2’-deoxycoformycin. Cancer Res 36:1481–1485PubMedGoogle Scholar
  9. 9.
    Ranganathan R, Larwood D (1978) Facile conversion of adenosine into new 2’-substi- tuted-2’-deoxy-arabinofuranosyladenine derivatives: Stereospecific synthesis of 2’-azi- do-2’-deoxy-, 2’-amino-2’-deoxy-, and 2’-mercapto-2’-deoxy-β-D-arabinofuranosylade- nines. Tetrahedron Lett 45:4341–4344CrossRefGoogle Scholar
  10. 10.
    Robins MJ, Hawrelak SD (1978) Nucleic acid related compounds. 28. 2’-Amino-araA 9-(2-amino-2-deoxy-β-D-arabinofuranosyl)adenine. Synthesis via nucleoside-aziridine or azido intermediates and biological effects. Tetrahedron Lett 39:3653–3656CrossRefGoogle Scholar
  11. 11.
    Unger FM, Christian R, Waldstatten P (1979) Azido- und Diazido-Derivative von Arabinonukleosiden. Tetrahedron Lett 7:605–608CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1980

Authors and Affiliations

  • M. Bobek
  • Y.-C. Cheng
  • E. Mihich
  • A. Bloch

There are no affiliations available

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